The vertebrate taxonomy ontology: a framework for reasoning across model organism and species phenotypes.

BACKGROUND: A hierarchical taxonomy of organisms is a prerequisite for semantic integration of biodiversity data. Ideally, there would be a single, expansive, authoritative taxonomy that includes extinct and extant taxa, information on synonyms and common names, and monophyletic supraspecific taxa that reflect our current understanding of phylogenetic relationships. DESCRIPTION: As a step towards development of such a resource, and to enable large-scale integration of phenotypic data across vertebrates, we created the Vertebrate Taxonomy Ontology (VTO), a semantically defined taxonomic resource derived from the integration of existing taxonomic compilations, and freely distributed under a Creative Commons Zero (CC0) public domain waiver. The VTO includes both extant and extinct vertebrates and currently contains 106,947 taxonomic terms, 22 taxonomic ranks, 104,736 synonyms, and 162,400 cross-references to other taxonomic resources. Key challenges in constructing the VTO included (1) extracting and merging names, synonyms, and identifiers from heterogeneous sources; (2) structuring hierarchies of terms based on evolutionary relationships and the principle of monophyly; and (3) automating this process as much as possible to accommodate updates in source taxonomies. CONCLUSIONS: The VTO is the primary source of taxonomic information used by the Phenoscape Knowledgebase (http://phenoscape.org/), which integrates genetic and evolutionary phenotype data across both model and non-model vertebrates. The VTO is useful for inferring phenotypic changes on the vertebrate tree of life, which enables queries for candidate genes for various episodes in vertebrate evolution

Dissociations between motor timing, motor coordination, and time perception after the administration of alcohol or caffeine

RATIONALE: The impacts of psychoactive drugs on timing have usefully informed theories of timing and its substrates. OBJECTIVES: The objectives of the study are to test the effects of alcohol and caffeine on the explicit timing involved in tapping with the implicit timing observed in the coordinated picking up of an object, and with the temporal discrimination. MATERIALS AND METHODS: Participants in the "alcohol" experiment (N = 16) received placebo, "low" (0.12 g/kg or 0.14 g/kg for women/men, respectively) or "high" (0.37 g/kg or 0.42 g/kg, respectively) doses of alcohol, and those in the "caffeine" experiment (N = 16) received placebo, 200 or 400 mg caffeine. Time production variability was measured by repetitive tapping of specified intervals, and sources of variance attributable to central timer processes and peripheral motor implementation were dissociated. The explicit timing in tapping was compared with the implicit timing in the coordinated picking up of an object. Time perception was measured as discrimination thresholds for intervals of similar duration. Drug effects on reaction time were also measured. RESULTS: For tapping, alcohol significantly increased timer variability, but not motor variability; it did not affect coordination timing in the grip-lift task. Conversely, for time perception, the low dose of alcohol improved temporal discrimination. Caffeine produced no effects on any of the timing tasks, despite significantly reducing reaction times. CONCLUSIONS: The effects of alcohol argue against a common clock process underlying time interval perception and production in the range below 1 s. In contrast to reaction time measures, time perception and time production appear relatively insensitive to caffeine

The role of interferon-γ, nitric oxide and lipopolysaccharide in intestinal graft-versus-host disease developing in F(1)-hybrid mice

(C57BL/6 × DBA/2) F(1)-hybrid mice injected with lymphoid cells from wild-type, C57BL/6 donors develop acute, lethal graft-versus-host disease (GVHD) in which the intestine is a major target. In its destructive phase intestinal GVHD is characterized by apoptosis of intestinal crypt epithelial cells and the development of endotoxaemia. Injection of as little as 10 μg endotoxin is lethal in mice with acute GVHD, and associated with the release of large amounts of tumour necrosis factor-α (TNF-α) into the serum. To explore the role of interferon-γ (IFN-γ) in the pathogenesis of intestinal GVHD we used IFN-γ gene knockout (gko) mice as donors. Recipients of grafts from these donors did not develop intestinal GVHD and, unlike recipients of wild-type grafts, did not die when injected with lipopolysaccharide (LPS). We also found that injection 10 μg LPS into recipients of wild-type grafts induced apoptosis of intestinal epithelial crypt cells and was associated with a burst of nitric oxide production in the intestine. Administration of N(ω)nitro l-arginine methyl ester blocked this response. In contrast, LPS did not induce either intestinal epithelial cell apoptosis or increased nitric oxide production in recipients of IFN-γ gko grafts. These findings indicate that donor-derived IFN-γ is instrumental for the development of intestinal GVHD. In a previous study we showed that recipients of IFN-γ gko grafts develop high levels of LPS-induced TNF-α release. When our current data are viewed in the context of this observation, they suggest that intestinal epithelial cell apoptosis in the parent→F(1)-hybrid model of acute GVHD is mediated primarily by nitric oxide rather than TNF-α, and that this depends on donor-derived IFN-γ